tbuckley/cabot-search huggingface dataset:
County-level food insecurity to predict cancer incidence and mortality in the United States, 2015-2020.
Authors: Krista Y. Chen, Amanda L. Blackford, S. M. Qasim Hussaini
Journal: Journal of Clinical Oncology (2023)

10539 Background: Modifiable dietary patterns incorporating inexpensive, calorie-dense, processed foods and meals low in fiber and other nutrients are associated with development of cancer. Inadequate access to quality nutrition is a crucial but underappreciated social determinant of health and predictor of poor cancer outcomes. We investigated the impact of county-level food insecurity on age-adjusted incidence and mortality rates (AAIR, AAMR) for all cancers. Methods: We linked county-level cancer incidence and mortality rates for 2015-2020 from NCI State Cancer Profiles to food insecurity measures from Feeding America and County Business Patterns. Measures included percentage of individuals experiencing food insecurity (as defined by USDA), percentage on Supplemental Nutrition Assistance Program (SNAP) benefits, average cost per meal, and density of fast-food restaurants. AAIR and AAMRs of all cancers per 100,000 individuals were compared between 1 st and 4 th quartiles for each measure using robust linear regression models with log transformation and population weights. Results: There was an annual average of 1,728,431 cancer diagnoses with AAIR 449 and 599,666 deaths with AAMR 149. Highest AAIRs were observed in &gt;50y (1351), men (488), non-Hispanic Whites (467), and urban counties (459). This differed from highest AAMR groups including &gt;50y (502), men (178), non-Hispanic Blacks (175), and rural counties (168) suggesting factors of increased disease severity or decreased access to care in the latter. Both AAIRs and AAMRs increased significantly when moving from least to most insecure counties, as defined by overall food insecurity, higher proportion of population on SNAP, higher fast-food density, and lower meal cost. AAMRs and AAIRs for lung cancer and CRC, and for rural residents were most exacerbated by changes in all measures of food insecurity, even when adjusting for screening rates for CRC in low access areas. Conclusions: Our study highlights the most food insecure counties have higher cancer incidence and even greater mortality burden. We recognize food insecurity as a proxy for socioeconomic disadvantage prior to and during cancer treatment. These results encourage prioritization of policies that optimize food assistance programs and clinical practices that incorporate food insecurity-related screenings in care delivery models. [Table: see text]
Tebentafusp (tebe) in a real-world cohort of 72 French metastatic uveal melanoma (UM) patients (pts).
Authors: Sophie Piperno-Neumann, Leah Mailly-Giacchetti, Toulsie Ramtohul, Mathilde Saint-Ghislain, Marc Pracht, Jean Christophe Thery, Pierre Combe, Noemie Litrowski, Hélène Martin, Caroline Dutriaux, Agathe Garcia, Leanne de Koning, Vincent Servois, Manuel Rodrigues
Journal: Journal of Clinical Oncology (2023)

e21583 Background: Up to 50% of UM pts will develop metastases with poor overall survival (OS) and limited treatment options. Tebe, a bispecific T-cell engager binding CD3 and the gp100 protein presented by the HLA A*02-01, recently showed a benefit in overall response rate (ORR), progression-free survival (PFS) and OS in HLA A*02-01 pos metastatic UM (mUM) pts in the IMCgp100-202 phase III trial. Prior to the EMA approval, French Health Authorities allowed an early access to tebe in May 2021 to UM metastatic pts. We here report our real-world experience with tebe in metastatic UM pts. Methods: Ongoing ambispective cohort of mUM pts treated with tebe in France. Metastases are evaluated according to RECIST 1.1 with assessments every 12 weeks (liver MRI +/- CT-scan). ORR, PFS, OS and toxicities are retrieved. Results: 72 pts started tebe between May 26 th 2021 and December 12 th 2022 (29 men and 43 women). Median age was 61 yo (32-78). Thirty, 34 and 7 patients underwent enucleation proton beam therapy or brachytherapy, respectively (one pt did not receive local treatment). The median time to first metastasis was 24 months (0-276). Tebe was prescribed in first-line in 46 patients, in second-line or more in 26 patients. Metastatic sites at tebe initiation were liver, lung, skin, bone and muscle in 71, 4, 2, 3 and 2 patients, respectively. Liver was the sole metastatic site in 63/72 patients (87.5%). With a median follow-up of 44 weeks, patients received a median of 36 weeks of tebe. Thirty patients discontinued tebe because of disease progression, two because of poor health status and none for toxicity. Of 60 assessable pts, 33 (55%) pts showed stable disease and 5 (8%) showed partial response as best response according to RECIST 1.1. Median PFS was 28 weeks (confidence interval 95% [CI95%]: 8-56) in the global cohort. OS at 12 months was 74% ([CI95%] = 0.62-0.89) in the global cohort, 73% ([CI95%] = 0.55-0.99) and 74% ([CI95%] = 0.57-0.97) in 1 st and 2 nd line and more, respectively. To date, 13 pts died. Circulating tumor DNA analyses and monitoring of peripheral blood leukocytes are ongoing and will be available by June 2023. Conclusions: In this ongoing, real-world, cohort of metastatic UM pts, tebe is associated with similar clinical outcomes as in the IMCgp100-202, phase III trial. Translational studies on blood and tumor samples are ongoing to identify predictive biomarkers of clinical benefit to this drug.
Phase 1b/2 study of abemaciclib combined with chemoimmunotherapy in pediatric and young adult patients with relapsed/refractory neuroblastoma (JPCS Part C).
Authors: Emily Gustava Greengard, Melissa Bear, Bradley DeNardo, Noah Federman, Julie Krystal, Giselle Linda Saulnier Sholler, Yanhong Zhou, Holly Knoderer, Sarah C Nabinger, Lindsey M. Hoffman
Journal: Journal of Clinical Oncology (2023)

TPS10068 Background: Survival for high-risk neuroblastoma (NBL) remains poor with over 50% of patients experiencing disease relapse. The addition of dinutuximab (DIN) and granulocyte macrophage colony-stimulating factor (GM-CSF) to irinotecan (IRN) and temozolomide (TMZ) in patients with first relapse achieved an overall response rate of 42% in the study ANBL1221 1 and is now standard of care. However, there remains a significant unmet need to improve outcomes for children with relapsed/refractory NBL. Deregulation of the Cyclin D/cyclin-dependent kinase (CDK) 4 &amp; 6 pathway has been observed in NBL, rendering CDK4 &amp; 6 inhibition logical to explore. Abemaciclib is an orally administered, selective CDK4 &amp; 6 inhibitor approved to treat breast cancer. JPCS (NCT04238819) is designed to assess the pharmacokinetics, safety, and tolerability of abemaciclib added to standard treatment regimens for relapsed/refractory pediatric solid tumors. Part A defined the recommended phase 2 dose (RP2D) of abemaciclib in combination with IRN and TMZ. In Part C, the addition of DIN + GM-CSF to the JPCS Part A regimen will be evaluated. The co-primary objectives of Part C are to determine the RP2D and to estimate the anti-tumor activity of abemaciclib added to the ANBL1221 chemoimmunotherapy backbone in patients with first relapse/refractory NBL. Methods: JPCS Part C is a two-stage, non-randomized, open-label, Phase 1b/2 study for patients &lt; 21 years of age with first relapse/refractory NBL. Stage 1 aims to identify the maximum tolerated dose (MTD) of abemaciclib at a starting dose of 55 mg/m 2 combined with DIN, GM-CSF, IRN and TMZ using a 3+3 design. One dose de-escalation (30 mg/m 2 ) will be possible if the starting dose is not tolerated. Further tolerability and initial anti-tumor activity will be evaluated in an expansion cohort at the MTD. Up to 11 evaluable patients will enroll in Stage 1 at the MTD; the MTD will be declared the RP2D if adequate safety and tolerability are observed and ≥6 patients achieve minimal response or better per International Neuroblastoma Response Criteria (INRC). Following determination of the RP2D, Stage 2 will enroll 35 patients. If ≥26 of 46 total patients achieve an INRC minimum response or better, further investigation of this regimen could be warranted. As of 31 Jan 2023, Part C is open for enrollment at one site (US) and additional sites are being evaluated. References: Mody et al. J Clin Oncol. 2020;38(19):2160-2169. Clinical trial information: NCT04238819 .
Low dose anti-PD(L)-1: A potentially effective alternative for greater accessibility in solid malignancies.
Authors: Iza Andrade de A. Souza, João Pedro Homse Netto, Barbara Garcia São José, Kathia Abdalla, Marina Topanotti, Fabio Leite Couto Fernandez, João Daniel Cardoso Guedes, Aline Fusco Fares, Daniel Vilarim Araujo
Journal: Journal of Clinical Oncology (2023)

e21523 Background: Anti-PD(L)1 agents changed the treatment landscape of multiple tumor types yielding long-term responses in a significant proportion of patients. However, these drugs are costly and not accessible to patients from most countries. Mounting data suggest that lower doses of anti-PD(L)1 can be as efficacious as label-approved doses at lower costs. Herein we compare the outcomes of patients treated with low-dose anti-PD(L)1 agents (LD) and patients treated with conventional doses (CD) at a single tertiary hospital. Methods: This is an observational historical cohort study evaluating the outcomes of patients treated with anti-PD(L)-1 agents (either at LD or CD) at Hospital de Base, São José do Rio Preto - Brazil. We included patients older than 18yo, with solid malignancies and treated with any anti-PD(L)1 agent. Patients were classified as having received LD if the dose administered at the first cycle was below the label dose. Data were abstracted from electronic medical records. Efficacy outcomes, including overall survival (OS), progression-free survival (PFS), and overall response rate (ORR), were evaluated. Log-rank test and Chi-square or Fisher's exact test were used as appropriate. A p-value of 0.05 was considered statistically significant. Results: From January 2020 to October 2022, a total of 43 patients were included: 26 (60.4%) received LD and 17 (39.6%) received CD. The mean age of LD and CD was 66.9 (SD 14.5) and 64.8 (SD 9.7), respectively. Most patients presented with ECOG 0 or 1 (64% LD and 66% CD), had metastatic disease at treatment onset (92% LD and 94.1% CD), and were treated in the first line (50% LD and 64% CD). Most frequent tumor sites were melanoma (38.5% LD, 56.3% CD) and lung (29.9% LD, 18.8% CD). Only 23.1% and 17.6% of tumours in LD and CD were tested for PD-L1 expression, of which 83% and 33% had PD-L1 &gt; 1. Most patients from both groups were treated with pembrolizumab (92.3% LD and 82.4% CD). The mean dose of pembrolizumab was 89.6 mg (1.5 mg/kg) for LD and 171 mg (2.1 mg/kg) for CD. After a median follow-up of 23 months, there was no significant difference in median OS (mOS), mPFS, and ORR between LD and CD (Table). A sensitivity analysis with patients receiving pembrolizumab was performed and had similar results (Table). Conclusions: Our study suggests there is no difference between patients treated with LD and CD anti-PD(L)1 in terms of OS, PFS, and ORR. The numerically shorter OS and PFS in the CD group may be due to selection bias and should be interpreted cautiously. LD anti-PD(L)1 could be an alternative to expand access in places where CD is not affordable. [Table: see text]
Molecular characterization of nectin-4 in non-small cell lung cancer subtypes.
Authors: Robert Hsu, Nishant Gandhi, Chul Kim, Hirva Mamdani, Balazs Halmos, Ari M. Vanderwalde, Matthew James Oberley, Patrick C. Ma, Stephen V. Liu, Jorge J. Nieva
Journal: Journal of Clinical Oncology (2023)

e21119 Background: Nectin-4 (Nectin cell adhesion molecule-4) is a tumor associated antigen overexpressed in multiple solid tumor types. Studies show that over 60% of NSCLC are nectin-4 overexpressed. As enfortumab vedotin, an antibody-drug conjugate directed against nectin-4, has been FDA approved for advanced urothelial carcinoma, this holds treatment implications. Here, we investigated nectin-4 expression in NSCLC subtypes. Methods: 27,607 NSCLC tumors were tested for whole transcriptome sequencing (WTS, NovaSeq) and NextGen DNA sequencing (592 gene panel or whole exome sequencing, WES) at Caris Life Sciences (Phoenix, AZ). Tumors were analyzed overall in quartiles by nectin-4 expression (Q4-greatest, Q1-least) and further analyzed in the adenocarcinoma (AD) and squamous carcinoma (SQ) cohorts. PD-L1 expression was tested by IHC (Dako 22C3). Immune cell populations were estimated by QuanTISeq. Statistical significance was determined using Chi-square/Fisher-Exact/Mann-Whitney U tests and adjusted for multiple comparisons (q &lt; 0.05). Results: We saw significantly greater expression of nectin-4 in SQ (median TPM- 15.68) versus AD tumors (median TPM - 9.88) (p &lt; 0.05). We saw a greater prevalence of NFE2L2, STK11, ERBB2 mutations and genomic loss of heterozygosity (LOH) but a lower percentage of PD-L1+ tumors in Q4 vs Q1 tumors (all q-value &lt; 0.05, Table 1). mRNA expression of immune checkpoints PDL1, CTLA4, CD80, CD86, HAVCR2, and IDO1 was increased in Q4 tumors (1.1-1.3-fold, all q &lt; 0.05). Q4 tumors had reduced estimates of M1 macrophages, regulatory T cells (Tregs), and CD8+ T cells and increased estimates of neutrophils and NK cells. The association of nectin-4 expression with the immune landscapes of AD and SQ was similar. Q4 tumors in AD and SQ displayed increased expression of the above-mentioned immune checkpoints (q &lt; 0.05). In AD and SQ, estimates of M1 macrophages, Tregs, and CD8+ T cells were reduced, but neutrophils and NK cells were increased in Q4 tumors (q &lt; 0.05). The pattern of molecular alterations was different in AD and SQ. While KEAP1, STK11 and ERBB2 mutations were significantly enriched in AD Q4 tumors, NFE2L2 mutations were significantly enriched in SQ Q4 tumors (Table 1). Prevalence of LOH was higher and PD-L1+ tumors was lower in Q4 tumors in both AD and SQ (Table 1). Conclusions: NFE2L2 alterations in SQ and STK11, KEAP1 mutations in AD, which are associated with poor immunotherapy (IO) response, were enriched in Q4 tumors. This suggests that the immune landscape associated with high nectin-4 expression in NSCLC may be driven by the dysregulated KEAP1-NFE2L2 pathway. Targeted therapy towards nectin-4 may benefit these NSCLC subtypes that do not respond well to IO. [Table: see text]
Impact of systemic immune-inflammation index in patients with limited-stage small cell lung cancer.
Authors: Ziling Zhang, Juan Li, Huijuan Liu, Yuxiang Wang, Xiaomei Li, Fangfei Jia, Junpeng Wen, Yan Zhao
Journal: Journal of Clinical Oncology (2023)

e20626 Background: The systemic immune-inflammation index (SII) has been suggested as a prognostic marker in several solid malignant neoplasms. However, there are few studies on the prognostic value of SII in patients with limited-stage SCLC. This study explored the impact of SII on overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer, and compared the predictive ability of SII and platelet/lymphocyte ratio (PLR) to find a better prognostic marker. Methods: In total, 572 patients with new diagnosis of limited-stage SCLC were included in this study. The optimal threshold of SII and PLR were determined using the outcome(OS)-based method by maximizing the log-rank test statistic and the survival differences.The predictive ability of SII and PLR were compared by drawing the continuous time-dependent receiver operating characteristic curves (time-dependent ROC). Logistic multivariable analysis was performed to identify factors associated with high SII. Propensity score matching (PSM) was used to balance confounders between groups and adjust observed selection bias. Kaplan-Meier methods and Cox proportional hazards models were used to assess the impact of pre-treatment SII on OS and PFS. Results: The median age of the whole group was 60.0 (25.0-81.0) years, and the median follow-up time was 56.5 (2.5-95.4) months. The optimal cutoff value of SII and PLR were 760.6 and 137.3, respectively. The area under the time-dependent ROC curves of SII and PLR in 1-, 2- and 3-year were 0.727, 0.708, 0.680 and 0.680, 0.669, 0.649, respectively. The high SII group was correlated with pleural effusion (P = 0.001), T stage (P = 0.009), N stage (P = 0.048), and pretreatment serum sodium (P = 0.003). The median OS and PFS of the whole group was 26.0 months (95%CI 23.8-28.2) and 13.0 months (95%CI 11.3 -14.7), and the 1-, 3-, 5-year OS rates and the 1-, 3-, 5-year PFS rates were 81.1%, 35.5%, 27.1% and 52.8%, 24.8%, 19.9%, respectively.There were 414 patients after PSM. In multivariable survival analysis, SII remained an independent prognostic factor for OS (HR1.792; 95%CI 1.416-2.268; P &lt; 0.001) and PFS (HR1.410; 95%CI 1.043-1.906; P = 0.025). Conclusions: Elevated SII is an independent adverse prognostic factor in patients with limited-stage SCLC and is superior to PLR in terms of prognostic ability.
Time trend on breast cancer mortality: How are we allocating physicians to deal with the disease in men and women in Brazil?
Authors: Jean Henri Schoueri, Luis Eduardo Werneck De Carvalho, Claudia Vaz De Melo Sette, Luiz Carlos de Abreu, Fernando Luiz Affonso Fonseca, Laercio da Silva Paiva, Fernando Adami
Journal: Journal of Clinical Oncology (2023)

e22532 Background: Female breast cancer (FBC) is a well-known public health issue worldwide. However, male breast cancer (MBC) is a rare condition, which might be overlooked by public health authorities and clinicians alike. Methods: Ecological study conducted with secondary data from 2008-2020 to examine the relationship between the amount of doctors per inhabitant on FBC and MBC mortality in Brazil and its federative regions. All data were gathered from Brazil’s public health system. For each cancer, mortality was analyzed by age and standardized by the World Health Organization’s population. The number of physicians was obtained from the Unified Health System and was calculated as the rate per 100,000 inhabitants. Linear regression was performed using stepwise selection/backward elimination. Results: Despite not reaching statistical significance, the total amount of physicians that work in the Unified Health System (UHS) was positively associated with MBC mortality (β 0.00003, IC95% -5,77 x 10 -6 ; 0.00007, p = 0.097), whereas there was a clear trend on FBC mortality reduction over the years (β -0.157, IC95% -0.2355;, p &lt; 0.001) and with higher number of gynecologists (β -0.0400, IC95% -0.577; -0.2236, p &lt; 0.001). Also, FBC mortality rates were positively associated with higher availability of physicians in general (β 0.0088, IC95% 0.0079; 0.0098, p &lt; 0.001) in the UHS. Conclusions: Trends on FBC and MBC mortality rates differ in Brazil. Whereas higher mortality was associated with a greater amount of doctors per inhabitant, perhaps due to more diagnosis, trends on lower mortality rates were found only for FBC – in those cases, it was associated with more gynecologists available. For both neoplasms, there was no association between mortality rates and the amount of clinical oncologists nor primary care physicians available in the country. [Table: see text]
Comprehensive genomic profiling and individual therapeutic planning in high-risk/refractory pediatric solid tumors: A single-center real-world study.
Authors: Ondrej Slaby, Petra Pokorna, Hana Pálová, Michal Kyr, Peter Múdry, Jaroslav Sterba
Journal: Journal of Clinical Oncology (2023)

10035 Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden ( &gt; 10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed and approved at multidisciplinary molecular tumor boards. Conclusions: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.
Trends of female representation in ASCO leadership and abstracts authorship: A detailed review.
Authors: Razan Aljaras, Ahmad Karkash, Vidya Sree Dandu, Ahmad Abdelfattah Alhader
Journal: Journal of Clinical Oncology (2023)

e23010 Background: Gender inequalities in medicine are ongoing challenges facing health care providers in different fields. Gender bias in medicine is gaining more attention, raising the awareness of this important topic. Per ASCO 2022 snapshot, females represent 35.8% of total oncologists in the United States. This study aims to spot the light on female representation in ASCO abstracts authors and presidents, adding to the continuous efforts aiming to achieve gender equity in the oncology practice. Methods: Data from the ASCO database and conference materials was gathered for analysis in the different categories. These categories included presidents of ASCO since it was founded in 1964 through 2022, and first authors in abstracts accepted over the past 5 years (2018-2022). Statistical analyses on first authors data were conducted, and a P-value of &lt; 0.001 was deemed to be statistically significant. Results: In the 58-year period (1964-2022), ASCO had 49 men (85%) and 9 women (15%) serve as presidents. 7 out of 9 total female presidents were elected in the last 20 years. In the 5 year period (2018-2022), there was a significant increase in the percentage of abstracts accepted for a female author. 37.1% of the presenters in 2018 were females, compared to 41.4% in 2022, with statistically significant results (P value &lt; 0.001), detailed percentages are shown in tables. Conclusions: Gender gap in the field of oncology goes beyond pay differences to include leadership positions and research authorship. But as shown by our analysis, there has been an increase in representation of females in ASCO abstracts authorship and leadership over the past years. Nonetheless, further work is needed to identify factors contributing to lower representation of women in oncology, and suggested solutions. [Table: see text][Table: see text]